CN103922983A - Process for catalytically synthesizing N-acylated sulfoximine compound - Google Patents
Process for catalytically synthesizing N-acylated sulfoximine compound Download PDFInfo
- Publication number
- CN103922983A CN103922983A CN201410142342.7A CN201410142342A CN103922983A CN 103922983 A CN103922983 A CN 103922983A CN 201410142342 A CN201410142342 A CN 201410142342A CN 103922983 A CN103922983 A CN 103922983A
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- synthetic method
- formula
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for catalytically synthesizing an N-acylated sulfoximine compound. The method comprises the following steps: adding an organic solvent and N-chloro-S-methyl-S-phenyl sulfoximine into an industrial reaction kettle, uniformly stirring and dissolving; adding substituted methylbenzene, tert-butyl hydroperoxide and a catalyst into the mixed solution, stirring and heating; adding a reaction auxiliary, and reacting under the condition of heat preservation; naturally cooling to room temperature after the reaction is finished; filtering, washing with ethyl acetate, carrying out rotary distilling and concentrating; and separating and purifying residues through column chromatography to obtain a target product. The method can be used for preparing the N-acylated sulfoximine compound with high yield and high purity, and the compound has the advantages of high reaction yield, high purity, mild condition and the like, and has wide industrial production prospect and high market application values.
Description
Technical field
The present invention relates to a kind of synthetic method of sulfoximide compound, relate more specifically to a kind of process for catalytic synthesis of N-acidylate sulfoximide compounds, belong to organic chemical synthesis field.
Background technology
In recent decades; sulfoximide compounds and derivative thereof are as chiral auxiliary and part and be widely used in the middle of the forming process of asymmetric synthesis or multiple bond; especially the structural unit of N-acidylate sulfoximide is usually used as the active coupling agent of precursor of acyl chlorides or carboxylic acid; and itself is for building the part-structure fragment of clinical medicine bioactive molecule, thereby in effect organic, that medicine and other fields performance is very important.
At present, in prior art, there is related process or the method for many preparation N-acidylate sulfoximide compounds, be mainly divided into following several method:
M.Ramu Yaday etc. (" Sulfoximines:A Reusable Directing Group for Chemo-and Regioselective ortho C-H Oxidation of Arenes "; Chem.Eur.J.; 2012; 18; 5541-5545) reported the conventional preparation technology of the sulfoximide compound of two kinds of N-protecteds; it adopts sulfoximide is that raw material is prepared corresponding target product with aryl carboxylic acid or aryl acyl chloride reaction, and its reaction formula is as follows:
Wang Long etc. (" The Copper-Catalyzed Oxidative N-Acylation of Sulfoximines "; Adv.Synth.Catal.; 2013; 355; 1490-1494) reported a kind of synthetic method of N-acidylate sulfoximide of copper catalysis; its adopt sulfoximide and aromatic aldehyde compound under the catalysis of CuBr through the oxidative coupling reaction of C-H/N-H double reaction course and prepare target product, the highest yield can reach 95%, its reaction formula is as follows:
Aswinkumar Garimallaprabhakaran etc. (" Boric Acid Mediated N-Acylation of Sulfoximines "; Synlett; 2011; 3; 361-364) reported and a kind ofly take boric acid and prepare the method for N-acidylate sulfoximide as catalyst sulfoximide and carboxylic acid reaction; it can be realized in reflux in toluene reaction, and reaction formula is as follows:
Although there is many synthesis techniques of N-acidylate sulfoximide analog derivative in prior art; yet; these methods are still not fully up to expectations for the use range of substrate; and reaction yield is not ideal enough, reaction conditions is also gentle not; have need low-temp reaction, have need pyroreaction; increase industrial cost, can not fully meet the needs of current industrial application.As can be seen here, how to expand the scope of application of reaction substrate, and further improve reaction yield and improve processing condition, this becomes the major issue of pendulum in face of organic chemist.
The problems that the inventor exists for prior art; through a large amount of literature research, it is experimental exploring; be intended to develop a kind of new catalytic synthesis technique of N-acidylate sulfoximide compounds; thereby reach the object that improves product yield, reduces production costs, fully meet the widespread demand of the synthetic application of current industrial.
Summary of the invention
In order to overcome above-mentioned pointed many defects, the inventor conducts in-depth research this, after having paid a large amount of creative works, thereby develops a kind of process for catalytic synthesis of N-acidylate sulfoximide compounds, and then has completed the present invention.
Particularly, technical scheme of the present invention and content relate to a kind of process for catalytic synthesis of N-acidylate sulfoximide compounds, described method comprises the steps: to add organic solvent and formula (I) compound N-chloro-S-methyl-S-phenylsulfone imines in industrial reaction still, be uniformly mixed dissolving, then in mixed solution, add successively formula (II) compound, tertbutyl peroxide and catalyzer, stir and heat up, add again reaction promoter, insulation reaction, react the complete room temperature that naturally cools to, after filtration, ethyl acetate washing, concentrated by rotary evaporation again, residue is crossed column chromatography separating purification, obtain formula (III) compound:
Wherein, R is selected from H, halogen, nitro, C independently of one another
1-C
6alkyl or C
1-C
6alkoxyl group;
N is the integer of 1-5.
In described synthetic method of the present invention, unless otherwise prescribed, from start to finish, the implication of halogen refers to haloid element, non-exclusively for example can be F, Cl, Br or I.
In described synthetic method of the present invention, unless otherwise prescribed, from start to finish, C
1-C
6the implication of alkyl refers to the straight or branched alkyl with 1-6 carbon atom, and it has comprised C
1alkyl, C
2alkyl, C
3alkyl, C
4alkyl, C
5alkyl or C
6alkyl, indefiniteness ground is such as can be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl or n-hexyl etc.
In described synthetic method of the present invention, unless otherwise prescribed, from start to finish, C
1-C
6alkoxyl group refers to " C defined above
1-C
6alkyl " group after being connected with O atom.
In described synthetic method of the present invention, the integer that n is 1-5, for example, can be 1,2,3,4 or 5, and the meaning is on phenyl ring, to have 1-5 the substituent R of independently selecting separately.
In described synthetic method of the present invention, described catalyzer is iron carbonyl compound, and described iron carbonyl is Fe
2(CO)
9, Fe (CO)
5, any one in cyclooctatetraene iron tricarbonyl, be preferably Fe
2(CO)
9.
In described synthetic method of the present invention, described reaction promoter is the mixture of silica reagent and ionic liquid, and wherein the mass ratio of silica reagent and ionic liquid is 1:1-1.5, preferably 1:1.
In described synthetic method of the present invention, described silica reagent is Et
2siH
2(diethylsilane), Ph
2siH
2(diphenyl silane), PhSiH
3(phenyl silane), (EtO)
2any one in MeSiH (diethoxymethyl silane), is preferably (EtO)
2meSiH.
In described synthetic method of the present invention, described ionic liquid is any one in 1-ethoxyethyl group-3-Methylimidazole Bromide, 1-methoxy ethyl-3-Methylimidazole chlorate, 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate, is preferably 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate.
In described synthetic method of the present invention, described formula (I) compound and (II) mol ratio of compound are 1:3-6, for example, can be 1:3,1:3.5,1:4,1:4.5,1:5,1:5.5 or 1:6, are preferably 1:4.5-5.5.
In described synthetic method of the present invention, the mol ratio of described formula (I) compound and tertbutyl peroxide is 1:4-5, can be to indefiniteness 1:4.1,1:4.2,1:4.3,1:4.4,1:4.5,1:4.6,1:4.7,1:4.8,1:4.9 or 1:5, be preferably 1:4.4-4.8.
In described synthetic method of the present invention, the ratio of described formula (I) compound and organic solvent does not have strict restriction, for example both molecular volumes ratio can be 1:4-6mol/L, be that the chloro-S-methyl-S-of every 1mol N-phenylsulfone imines is used 4-6L solvent, for example can be 1:4mol/L, 1:4.5mol/L, 1:5mol/L, 1:5.5mol/L or 1:6mol/L, be preferably 1:5mol/L.
In described synthetic method of the present invention, described formula (I) compound compares 1:10-14mol/g with the molar mass of catalyzer, be that the chloro-S-methyl-S-of every 1mol N-phenylsulfone imines is used 10-14g catalyzer, can be to indefiniteness 1:10mol/g, 1:11mol/g, 1:12mol/g, 1:13mol/g or 1:14mol/g.
In described synthetic method of the present invention, described formula (I) compound compares 1:15-20mol/g with the molar mass of reaction promoter, be that the chloro-S-methyl-S-of every 1mol N-phenylsulfone imines is used 15-20g reaction promoter (quality of reaction promoter is the total mass of silica reagent and ionic liquid) herein, can be to indefiniteness 1:15mol/g, 1:16mol/g, 1:17mol/g, 1:18mol/g, 1:19mol/g or 1:20mol/g.
In described synthetic method of the present invention, described organic solvent is any one in toluene, trichloromethane, acetonitrile, methyl alcohol, is preferably acetonitrile.
In described synthetic method of the present invention, temperature of reaction is 50-60 ℃, for example can be to indefiniteness 50 ℃, 51 ℃, 52 ℃, 53 ℃, 54 ℃, 55 ℃, 56 ℃, 57 ℃, 58 ℃, 59 ℃ or 60 ℃.
In described synthetic method of the present invention, the reaction times is 8-15h, can be to indefiniteness 8h, 9h, 10h, 11h, 12h, 13h, 14h or 15h.
In described synthetic method of the present invention, pentane/ethyl acetate mixed solution that the separated employing of column chromatography volume ratio is 2:1 is as elutriant (all adopting this elutriant in all embodiment below).
Compared with prior art, beneficial effect of the present invention is:
1, developed novel reaction substrate for building the processing method of N-acidylate sulfoximide compound, and efficient catalyst system is provided.
2, reaction response auxiliary agent has significantly improved with catalyzer close fit the yield reacting.
3, the inventive method reaction conditions is gentle, the reaction times is short, has the huge advantage of large-scale production.
Embodiment
Below by specific embodiment, the present invention is described in detail; but the purposes of these exemplary embodiments and object are only used for exemplifying the present invention; not real protection scope of the present invention is formed to any type of any restriction, more non-protection scope of the present invention is confined to this.
Embodiment 1
In industrial synthesis reaction vessel, add 5L acetonitrile and 1mol formula (I) compound N-chloro-S-methyl-S-phenylsulfone imines, be uniformly mixed dissolving, then in mixed solution, add successively 5mol formula (II) compound, 4.5mol tertbutyl peroxide and 12g catalyst Fe
2(CO)
9, stir and to be warming up to 55 ℃, then add (EtO)
2meSiH and 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate be take the reaction promoter (both quality sums are 18g) that mass ratio is mixed to get as 1:1, insulation reaction 10h at this temperature, react the complete room temperature that naturally cools to, after filtration, ethyl acetate washing, then concentrated by rotary evaporation, residue is crossed column chromatography separating purification, obtain formula (III) compound, yield is 97.6%, and purity is 98.6% (HPLC), and the nuclear magnetic resonance data of product is as follows:
1H?NMR(400MHz,CDCl
3)δ=8.06(m,2H),7.97(m,2H),7.69(t,J=7.3Hz,1H),7.60(t,J=8.0Hz,2H),7.32(m,2H),3.45(s,3H),2.41(s,3H)。
Embodiment 2
In industrial synthesis reaction vessel, add 4.5L acetonitrile and 1mol formula (I) compound N-chloro-S-methyl-S-phenylsulfone imines, be uniformly mixed dissolving, then in mixed solution, add successively 5.5mol formula (II) compound, 4.8mol tertbutyl peroxide and 13g catalyst Fe
2(CO)
9, stir and to be warming up to 50 ℃, then add (EtO)
2meSiH and 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate be take the reaction promoter (both quality sums are 15g) that mass ratio is mixed to get as 1:1, insulation reaction 12h at this temperature, react the complete room temperature that naturally cools to, after filtration, ethyl acetate washing, then concentrated by rotary evaporation, residue is crossed column chromatography separating purification, obtain formula (III) compound, yield is 97.1%, and purity is 98.2% (HPLC), and the nuclear magnetic resonance data of product is as follows.
1H?NMR(400MHz,CDCl
3)δ=8.13(t,J=1.7Hz,1H),8.04(m,3H),7.71(tt,J=1.1,7.4Hz,1H),7.62-7.65(m,2H),7.46(ddd,J=1.1,2.1,7.4Hz,1H),7.34(t,J=7.8Hz,1H),3.45(s,3H)。
Embodiment 3
In industrial synthesis reaction vessel, add 5.5L acetonitrile and 1mol formula (I) compound N-chloro-S-methyl-S-phenylsulfone imines, be uniformly mixed dissolving, then in mixed solution, add successively 4.5mol formula (II) compound, 4.6mol tertbutyl peroxide and 14g catalyst Fe
2(CO)
9, stir and to be warming up to 60 ℃, then add (EtO)
2meSiH and 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate be take the reaction promoter (both quality sums are 16g) that mass ratio is mixed to get as 1:1, insulation reaction 15h at this temperature, react the complete room temperature that naturally cools to, after filtration, ethyl acetate washing, then concentrated by rotary evaporation, residue is crossed column chromatography separating purification, obtain formula (III) compound, yield is 96.8%, and purity is 98.9% (HPLC), and the nuclear magnetic resonance data of product is as follows.
1H?NMR(600MHz,CDCl
3)δ=8.30(d,J=8.9Hz,2H),8.23(d,J=8.9Hz,2H),8.05(dd,J=0.8,8.2Hz,2H),7.72(t,J=7.4Hz,1H),7.66(t,J=8.0Hz,2H),3.51(s,3H)。
Embodiment 4
In industrial synthesis reaction vessel, add 5L acetonitrile and 1mol formula (I) compound N-chloro-S-methyl-S-phenylsulfone imines, be uniformly mixed dissolving, then in mixed solution, add successively 5mol formula (II) compound, 4.4mol tertbutyl peroxide and 10g catalyst Fe
2(CO)
9, stir and to be warming up to 55 ℃, then add (EtO)
2meSiH and 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate be take the reaction promoter (both quality sums are 20g) that mass ratio is mixed to get as 1:1, insulation reaction 13h at this temperature, react the complete room temperature that naturally cools to, after filtration, ethyl acetate washing, then concentrated by rotary evaporation, residue is crossed column chromatography separating purification, obtain formula (III) compound, yield is 97.2%, and purity is 98.3% (HPLC), and the nuclear magnetic resonance data of product is as follows.
1H?NMR(400MHz,CDCl
3)δ=8.32(s,1H),8.03(m,1H),7.91(s,1H),7.59-7.71(m,5H),3.44(s,3H),2.35(s,3H)。
Embodiment 5-8
Remove catalyst Fe
2(CO)
9replace with outside following component, in the mode identical with embodiment 1-4, implemented respectively embodiment 5-8, the corresponding relation of component and experimental result is as shown in table 1 below:
Table 1
From embodiment 1-4 and table 1, the kind of catalyzer iron carbonyl has critical impact to reaction system catalytic performance, and the inventor has filtered out Fe by a large amount of experimental exploring
2(CO)
9as the optimal catalyst of reaction, its catalytic performance is obviously better than other iron carbonyl compound (as very similar Fe (CO)
5).
Embodiment 9-12
Remove (EtO) in reaction promoter
2meSiH replaces with outside following component, in the mode identical with embodiment 1-4, has implemented respectively embodiment 9-12, and the corresponding relation of component and experimental result is as shown in table 2 below:
Table 2
Embodiment 13-16
Except the 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate in reaction promoter is replaced with following component, in the mode identical with embodiment 1-4, implemented respectively embodiment 13-16, the corresponding relation of component and experimental result is as shown in table 3 below:
Table 3
Embodiment 17-20
Except not adding reaction promoter, in the mode identical with embodiment 1-4, implemented respectively embodiment 17-20, experimental result is as shown in table 4 below:
Table 4
"--" represents not add.
From embodiment 1-4 and table 2-4, reaction promoter component kind is also the key factor that affects material reactivity and catalyst activity, has studied the composite result of different compounds in each component, wherein only (EtO) by experiment of single factor
2the combination of MeSiH and 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate can impel reaction yield to reach more than 95%; And the combination of other silica reagent and ionic liquid all can not reach the technique effect of excellence like this.In addition, reaction promoter is synergistic catalyst system and increase the catalytic effect of reaction effectively, and when lacking the existing of reaction promoter, reaction yield significantly reduces, and this has confirmed the synergy between catalyzer and reaction promoter apparently.
In sum; the inventor is by a large amount of creative works; developed a kind of new catalytic technique of synthetic N-acidylate sulfoximide compound; it has been expanded the scope of reaction raw materials, has significantly improved reaction yield; and there is the advantages such as reaction conditions gentleness, reaction times be short, there is very wide industrial prospect and market application potential.
The purposes that should be appreciated that these embodiment only limits the scope of the invention for the present invention being described but not being intended to.In addition; also should understand; after having read technology contents of the present invention, those skilled in the art can make various changes, modification and/or modification to the present invention, within these all equivalent form of values fall within the protection domain that the application's appended claims limits equally.
Claims (10)
1. the process for catalytic synthesis of a N-acidylate sulfoximide compounds; described method comprises the steps: to add organic solvent and formula (I) compound N-chloro-S-methyl-S-phenylsulfone imines in industrial reaction still; be uniformly mixed dissolving; then in mixed solution, add successively formula (II) compound, tertbutyl peroxide and catalyzer; stir and heat up; add again reaction promoter; insulation reaction; react the complete room temperature that naturally cools to; ethyl acetate washing after filtration; concentrated by rotary evaporation again, residue is crossed column chromatography separating purification, obtains formula (III) compound:
Wherein, R is selected from H, halogen, nitro, C independently of one another
1-C
6alkyl or C
1-C
6alkoxyl group;
N is the integer of 1-5.
2. synthetic method as claimed in claim 1, is characterized in that: described catalyzer is iron carbonyl compound, and described iron carbonyl is Fe
2(CO)
9, Fe (CO)
5, any one in cyclooctatetraene iron tricarbonyl.
3. synthetic method as claimed in claim 1 or 2, is characterized in that: described reaction promoter is the mixture of silica reagent and ionic liquid, and wherein the mass ratio of silica reagent and ionic liquid is 1:1-1.5.
4. synthetic method as claimed in claim 3, is characterized in that: described silica reagent is Et
2siH
2, Ph
2siH
2, PhSiH
3, (EtO)
2any one in MeSiH.
5. the synthetic method as described in claim 3-4 any one, is characterized in that: described ionic liquid is any one in 1-ethoxyethyl group-3-Methylimidazole Bromide, 1-methoxy ethyl-3-Methylimidazole chlorate, 1-methoxy ethyl-3-methyl imidazolium tetrafluoroborate.
6. the synthetic method as described in claim 1-5 any one, is characterized in that: described formula (I) compound and (II) mol ratio of compound are 1:3-6, are preferably 1:4.5-5.5.
7. the synthetic method as described in claim 1-6 any one, is characterized in that: the mol ratio of described formula (I) compound and tertbutyl peroxide is 1:4-5, is preferably 1:4.4-4.8.
8. the synthetic method as described in claim 1-7 any one, is characterized in that: described formula (I) compound compares 1:10-14mol/g with the molar mass of catalyzer.
9. the synthetic method as described in claim 1-8 any one, is characterized in that: described formula (I) compound compares 1:15-20mol/g with the molar mass of reaction promoter.
10. the synthetic method as described in claim 1-9 any one, is characterized in that: described organic solvent is any one in toluene, trichloromethane, acetonitrile, methyl alcohol, is preferably acetonitrile.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410142342.7A CN103922983B (en) | 2014-04-10 | 2014-04-10 | A kind of catalysis synthesizing technology of N-acidylate sulfoximide compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410142342.7A CN103922983B (en) | 2014-04-10 | 2014-04-10 | A kind of catalysis synthesizing technology of N-acidylate sulfoximide compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103922983A true CN103922983A (en) | 2014-07-16 |
| CN103922983B CN103922983B (en) | 2016-02-03 |
Family
ID=51141409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410142342.7A Expired - Fee Related CN103922983B (en) | 2014-04-10 | 2014-04-10 | A kind of catalysis synthesizing technology of N-acidylate sulfoximide compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103922983B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109516937A (en) * | 2018-10-31 | 2019-03-26 | 成都理工大学 | A kind of synthetic method of sulphoxide imine acylate |
| CN113292466A (en) * | 2021-06-07 | 2021-08-24 | 江苏科技大学 | Sulfoxide imine enamine acid ester compound and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101328143A (en) * | 2008-07-30 | 2008-12-24 | 中国科学院上海有机化学研究所 | Fluorine-containing sulphoxide imines compounds, synthetic methods and uses sthereof |
| CN102816134A (en) * | 2012-08-03 | 2012-12-12 | 南开大学 | 1,2,3-thiadiazole-containing sulfilimine (sulfonimine) compounds and their preparation method and use |
-
2014
- 2014-04-10 CN CN201410142342.7A patent/CN103922983B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101328143A (en) * | 2008-07-30 | 2008-12-24 | 中国科学院上海有机化学研究所 | Fluorine-containing sulphoxide imines compounds, synthetic methods and uses sthereof |
| CN102816134A (en) * | 2012-08-03 | 2012-12-12 | 南开大学 | 1,2,3-thiadiazole-containing sulfilimine (sulfonimine) compounds and their preparation method and use |
Non-Patent Citations (2)
| Title |
|---|
| DANIEL L.PRIEBBENOW 等: "C-H activation of methyl arenes in the MnO2-mediated aroylation of N-chlorosulfoximines", 《ORGANIC LETTERS》 * |
| YADAV, M. RAMU等: "Sulfoximine Directed Intermolecular o-C-H Amidation of Arenes with Sulfonyl Azides", 《ORGANIC LETTERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109516937A (en) * | 2018-10-31 | 2019-03-26 | 成都理工大学 | A kind of synthetic method of sulphoxide imine acylate |
| CN113292466A (en) * | 2021-06-07 | 2021-08-24 | 江苏科技大学 | Sulfoxide imine enamine acid ester compound and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103922983B (en) | 2016-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110204487A (en) | A kind of synthetic method of quinoline | |
| CN106083716B (en) | A kind of preparation method of 3- aryl isoquinolines compound | |
| CN103922983B (en) | A kind of catalysis synthesizing technology of N-acidylate sulfoximide compounds | |
| CN104774174B (en) | A kind of method of asymmetric syntheses S carbinoxamines | |
| CN107445991A (en) | A kind of Phosphine ligands of indoles skeleton and its preparation method and application | |
| CN105237372A (en) | Catalytic synthesis method of drug intermediate aryl ketone compound | |
| CN105646382A (en) | Preparation method of 1,3,5-trisubstituted 1,2,4-triazole compound | |
| CN105085272A (en) | Synthesis method for aryl or heteroaryl ester compound | |
| CN105037073A (en) | Synthetic method for biaryl compounds | |
| CN105949119B (en) | A method of polysubstituted 2 (the 1H)-quinolinones compound of synthesis | |
| CN108864164A (en) | A kind of synthetic method of the 2- alkynyl Benzazole compounds of level-one amine guiding | |
| CN104610108B (en) | A kind of synthetic method of medicine for central nervous system Adrafinil midbody compound | |
| CN105237466A (en) | Method for compounding tri-substituted pyridine derivatives | |
| CN103896793B (en) | Synthesis method of amide compounds | |
| CN110563551A (en) | method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compound | |
| CN106243034B (en) | A kind of method that Pd/Ti is catalyzed four component carbonylation coupling reactions synthesis substd quinolines | |
| CN103880675A (en) | Improved catalyzed synthesis method for 1,4-dicarbonyl compound | |
| CN101531578B (en) | Method for preparing axial chirality diaromatic compound with optical activity | |
| CN102093354B (en) | Indolizine Mannich base compound and preparation method thereof | |
| CN107011218A (en) | A kind of fluorine nitrogen type amination reagent, its preparation method and application | |
| CN106928136A (en) | A kind of Graphene palladium cobalt sequential catalyst synthesizes the method for MK intermediate | |
| CN106232573A (en) | The method being prepared benzidine by aniline it is catalyzed by ruthenium | |
| CN103936672B (en) | A kind of synthetic method of medicine intermediate poly-substituted quinoline derivative | |
| CN105218553A (en) | A kind of synthetic method of pharmaceutical intermediate pyrrolo-indole compounds | |
| CN103864645A (en) | Disubstituted perfluoroalkyl phthalonitrile compound and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Pang Feng Inventor before: Li Na |
|
| COR | Change of bibliographic data | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20151218 Address after: 266033 No. 4 Renmin Road, Shandong, Qingdao Applicant after: Pang Feng Address before: 601, room three, unit 12, Jixiang building, Weifang Economic Development Zone, Shandong 261000, China Applicant before: Li Na |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160203 Termination date: 20170410 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |